Raspberry Polyphenol Extracts Modify Physiological Parameters and the Hepatic Transcriptome of C57BL/6J Mice Fed a High-Fat Diet

Abstract

Abstract Objectives Red raspberries are rich in polyphenols, fiber, and volatile compounds, and have been demonstrated to have favorable effects on energy homeostasis in mice. We made two extracts from red raspberries, enriched in either hydrophilic (R25) or hydrophobic (R80) polyphenols. We tested the hypothesis that these polyphenol extracts would differentially alter and improve physiological measures and the hepatic transcriptome of C57BL/6J male mice fed a obesigenic high fat diet (HF). Methods Raspberry polyphenol extracts were obtained using FPX-66 resin, and eluting with 25% (R25) and 80% (R80) ethanol (v/v); eluates were then dried. Mice were provided a low fat diet (LF, 10% kcal fat, n = 12), high fat diet (HF, 45% kcal fat, n = 12), HF with raspberry puree concentrate (RPC, n = 8), HF with R25 (n = 8), or HF with R80 (n = 8) ad libitum for 10 weeks. Body weights, food intake, and fasting glucose levels were measured. Post mortem, serum was collected for ELISA, organ weights were recorded, and liver tissue was collected for triglyceride analysis and differential expression analysis. Results Energy efficiency and liver weights in the R25 and R80 groups were intermediate to the LF and HF controls. Fasting blood glucose, serum triglycerides, and adipose tissue weights did not differ between treatment groups. A trend toward significance was seen in reduction of weight gain in the raspberry treatment groups. Differential gene expression analysis revealed that the R25 diet acted agonistically towards the constitutive androstane receptor (CAR) and reduced the relative levels of several sterol regulatory binding protein-regulated genes. Notably, the R80 diet robustly increased levels of Cyp4a14, a peroxisome proliferator-activated receptor alpha (PPAR-α)-regulated gene. Conclusions Supplementation of a high fat diet with raspberry polyphenol extracts modified hepatic gene expression and energy efficiency in C57BL/6J mice. The two extracts had a differential impact on hepatic gene expression. For example, the R25 extract behaved as an agonist for CAR, while the R80 extract behaved as an agonist for PPAR-α. These findings suggest that select polyphenols found within red raspberries may serve as nutraceuticals that specifically act via PPAR-α, CAR, and other targets in liver. Funding Sources National Processed Raspberry Commission and Washington Red Raspberry Commission.